The long term goal of this research is to functionally characterize the neuronal circuitry involved in the presynaptic control of the synaptic effectiveness of primary afferent fibers in the mammalian spinal cord, as well as the role played by presynaptic inhibition in sensory motor integration. To this end we will pursue the following specific aims: Specific Aim 1: In anesthetized or decerebrated cats we will study the possible specificity of the control exerted by cortico-spinal, reticulo-spinal and coeruleo-spinal fibers on the segmental pathways mediating the primary afferent depolarization (PAD) of single group Ia and Ib afferents according to the muscle of origin of the afferent fibers. The action of cortico-spinal inputs will be examined more extensively by studying the effects produced by microstimulation of the motor cortex on the intraspinal threshold of pairs of single Ia and/or lb fibers belonging to the same or to different muscles (flexors and extensors). In addition, studies will be made in decerebrate cats of changes in the PAD patterns of single Ia and Ib fibers before and after blocking impulse conduction in descending pathways by reversible cooling of the thoracic spinal cord. Specific Aim 2: In anesthetized cats, studies will be made on the PAD patterns of functionally identified muscle afferents before and after nerve section and regeneration. The hypothesis to be tested is that the PAD patterns observed in normal Ia and Ib fibers are reestablished after nerve lesions following appropiate reconnection of regenerated afferent fibers with peripheral receptors. Specific Aim 3: Pharmacological and electrophysiological studies of the synaptic actions exerted by last-order intermediate nucleus interneurons on group I afferent fibers and motoneurons will be made in anesthetized cats. Particular attention will be given to test the proposal that the inhibition of motoneurons produced by these interneurons is GABAergic. Studies will be made on the intraspinal distribution and functional characteristics of networks of dorsal horn neurons driving several classes of intermediate nucleus interneurons. Specific Aim 4: Studies will continued in anesthetized cats to further document the observation that during presynaptic inhibition of Ia monosynaptic EPSPs there is no effect on monosynaptic EPSPs produced by stimulation of descending fibers. By means of deconvolution techniques we will examine the effects of stretching synergistic and antagonistic muscles as well as of electrical stimulation of group I fibers on the amplitude and probability distribution of the discrete components of monosynaptic EPSPs produced in the same motoneuron by single Ia fibers and by a small number of descending fibers.